Study aims to reduce risk of asthma by treating infant atopic dermatitis

National report - A large, prospective, six-year clinical trial is well under way to investigate whether early, aggressive treatment of atopic dermatitis in infants can alter the future course of their skin disorder and the development of other manifestations of atopy, particularly asthma.

The study, launched last fall, is enrolling approximately 1,100 children ages 3 months to 18 months with a <3-month duration of atopic dermatitis and an immediate family member with atopic disease. The children are being randomized to initial double-blind treatment of active atopic dermatitis with pimecrolimus cream 1 percent (Elidel, Novartis) or vehicle. Management in both study arms allows for rescue as needed after three days with fluticasone propionate 0.05 percent (Cutivate, GlaxoSmithKline).

Treatment is continued until clearing is achieved, and restarted as needed. In addition, a bland emollient is being used routinely in all children.

"The incidence of eczema has quadrupled over the last 50 years, and that has paralleled the increasing incidence of asthma. It is exciting to think that through early effective management of atopic dermatitis, dermatologists may play a very important role not only in improving quality of life for atopic dermatitis patients and their families, but also in decreasing the risk of another life-altering and potentially life-threatening condition," says Amy S. Paller, M.D., a principal investigator and professor and chair, department of dermatology, Northwestern University Feinberg School of Medicine, Chicago.

Halting the march

The study is based on the theory that epicutaneous allergen sensitization through the disrupted atopic skin barrier amplifies a systemic allergic response that goes on to affect the upper and lower airways. According to that theory, allergens binding to Langerhans cells in the skin migrate to the lymph nodes, inducing excess IgE production and a pool of Th2 cells that enter the circulation to reach nasal and lung mucosa. In developing the protocol, the investigators are hypothesizing that early, aggressive treatment of atopic dermatitis with pimecrolimus will improve the skin barrier and thereby reduce epicutaneous allergen penetration and the cascade leading to development of asthma or allergic rhinitis.

"There are several lines of evidence supporting the concept that the risk of asthma may be controlled by early treatment of atopic dermatitis to reduce epicutaneous sensitization," says Jonathan M. Spergel, M.D., principal investigator and assistant professor, division of allergy and immunology, University of Pennsylvania School of Medicine, Philadelphia.

Mouse studies Some of the most compelling support comes from a mouse model allergy study performed by Dr. Spergel and colleagues showing an association between prior epicutaneous sensitization and subsequent systemic allergic responses and airway sensitization. In that investigation, animals sensitized to ovalbumin via its application under occlusion to tape-stripped skin developed histologic skin changes consistent with atopic dermatitis. In addition, compared with saline-treated controls, those animals manifested an increased systemic allergic response to inhaled ovalbumin as well as airway hyper-responsiveness to methacholine.

Other support for the concept that systemic allergen sensitization can be mediated through the skin derives from the observation that patients with atopic dermatitis have large numbers of circulating allergen sensitization cells, particularly CLA+ Th2 cells.

Furthermore, epidemiologic studies show that atopic dermatitis patients have not only an increased risk of developing asthma, they also have elevated serum IgE levels, and that earlier sensitization, higher IgE levels and greater atopic dermatitis severity correlate with an increased likelihood of developing asthma.

"Those relationships between atopic dermatitis and asthma risk suggest infants should be a target population for preventing asthma," Dr. Spergel says. "There have been some studies investigating a potential benefit of prophylactic antihistamine treatment in children with atopic dermatitis, but this study is unique in examining whether asthma risk can be modulated through better control of atopic dermatitis."